Thromb Haemost 2022; 122(09): 1621-1624
DOI: 10.1055/a-1772-1192
Letter to the Editor

Human Atheromatous Plaques Expressed Sensing Adaptor STING, a Potential Role in Vascular Inflammation Pathogenesis

Judith Pallarés*
1   Department of Pathology, Hospital Universitari Arnau de Vilanova, Lleida, Spain
,
Núria Torreguitart*
2   Department of Vascular Surgery, Hospital Universitari Arnau de Vilanova, Lleida, Spain
,
Gloria Arqué
3   Clinical Neurosciences Group, Institut de Recerca Biomèdica de Lleida (IRBLleida), Lleida, Spain
,
4   Department of Experimental Medicine, Institut de Recerca Biomèdica de Lleida (IRBLleida), Universitat de Lleida, Lleida, Spain
,
3   Clinical Neurosciences Group, Institut de Recerca Biomèdica de Lleida (IRBLleida), Lleida, Spain
5   Stroke Unit, Department of Neurology, Hospital Universitari Arnau de Vilanova, Medicine Department, Universitat de Lleida, Lleida, Spain
› Author Affiliations
Funding This study was supported by the Government of Catalonia-Agència de Gestió d'Ajuts Universitaris i de Recerca (FP: 2017 SGR 1628), Instituto de Salud Carlos III and co-funded by European Union (ERDF/ESF, “Investing in your future”) (F.P.: Project PI17-01725; M.P-.O.: PI20-0155), Diputació de Lleida and IRBLleida funds (PIRS call), and the INVICTUS plus Research Network (Carlos III Health Institute).

Introduction

Atherogenesis is a complex physiological process that involves inflammation, and it is a significant contributor to plaque development and plaque vulnerability. Immune activation can be behind the increased inflammation in atherosclerosis.[1] In many organisms, detecting foreign DNA is an essential part of immunity. The cyclic GMP–AMP synthase (cGAS)–stimulator of interferon genes (STING) pathway has emerged as an effective mechanism for connecting DNA sensing to the production of potent innate immune defense programs and it plays a substantial role in this process in mammalian cells.[2] The allosteric activation of cGAS' catalytic activity by binding to double-stranded DNA leads to the formation of 2′,3′-cyclic GMP–AMP (cGAMP), a second messenger molecule and potent agonist of STING. The activation of the cGAS–STING pathway is triggered by a fundamental constituent of life (particularly DNA), and it lacks any pathogen-specific characteristics, which distinguishes it from several other innate immune signaling mechanisms. As a result, cGAS identifies a wide range of DNA species, both foreign and self-derived.

Even though pathological process inducers are disease-specific, there is evidence for the cGAS–STING pathway's role as a driver of both (hyper-)acute and chronic, low-grade inflammatory states associated with a variety of illnesses.[3] This role is not unexpected due to its fundamental function as a ubiquitous and sensitive mechanism for out-of-context DNA recognition. Furthermore, preliminary evidence suggested that intracellular trafficking pathway abnormalities can significantly impact STING activity, and it contributes to inappropriate immune activation. Although chronic low-grade inflammatory stages have been associated with atherosclerosis, the cGAS–STING pathway has not been explored in this relevant pathophysiological process. Here, we explored the expression of STING protein in the artheriosclerotic (ATC) plaque of human patients who underwent carotid endarterectomy.

Author Contributions

F.P., N.T., and M.P-.O. conceived the study. G.A. and J.P. designed the experiments. N.T., J.P., G.A.: sample processing, data analysis, and data interpretation. G.A., F.P., and M.P-.O.: drafted the manuscript. M.P.O. and F.P. procured funding. All authors critically revised and approved the final version of the manuscript.


* These authors contributed equally to this work.


** These authors contributed equally to this work as senior authors.




Publication History

Received: 20 September 2021

Accepted: 12 February 2022

Accepted Manuscript online:
15 February 2022

Article published online:
05 May 2022

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